Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of patients with metastatic melanoma remains poor and there is a need to develop new regimens with low toxicity. We investigated a novel outpatient regimen combining oral and intravenous chemotherapy with daily subcutaneous bleomycin. Twenty-nine chemotherapy-naive patients with metastatic melanoma were treated with a novel regimen consisting of low dose lomustine, daily subcutaneous bleomycin, chlorambucil, methotrexate and vinblastine with tamoxifen for an 8 week cycle (LBCMVT-56). A median of two cycles were given until disease progression or grade 3/4 toxicity. Five out of 29 (17%) patients had an objective response, of whom two (7%) had a complete response and remain progression-free after 2 years of follow-up. The median overall survival was 7.3 months. A symptomatic response was seen in 11 out of 29 patients (38%). Toxicity was acceptable, with grade 3/4 haematological toxicity seen in 25% of cycles, infection requiring intravenous antibiotics in 11% of cycles, and pulmonary toxicity seen in 4% of cycles. Hospitalization was required in 21% of the patients at some point during the treatment, most commonly for neutropenic sepsis. LBCMVT-56 chemotherapy is a novel outpatient regimen producing occasional durable complete responses in a patient group with a poor prognosis. The median survival is similar to that obtained with dacarbazine, though the toxicity is greater.
Melanoma Res 2003 Apr
PMID:Low-dose continuous chemotherapy for metastatic melanoma: a phase II trial. 1269 Mar 5

The systemic side effects of isolated limb perfusion (ILP) with rhTNF alpha and melphalan are characterised by the induction of a systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was investigated with respect to its role in SIRS after TNF-ILP. Serum-PCT was analysed in 24 patients (12 male, 12 female), who treated by ILP for regionally metastasized melanoma (n = 8) or locally advanced soft tissue sarcoma (n = 16). Serum samples were analysed pre- and intraoperatively, and at defined intervals after reperfusion of the limb. In addition to PCT, serum IL-6 and IL-8 were analysed in 11 patients. PCT was significantly elevated over baseline after ILP with a maximum between 8 and 36 hours (p < 0.001). Even 96 hours after reperfusion, PCT was still significantly elevated as compared to baseline levels (p = 0.005). There was no correlation to the systemic leakage rate during the perfusion. IL-6 and IL-8 were also significantly increased after ILP (p = 0.001), but the maximum peaks of both cytokines were reached much earlier than for PCT (IL-8 max. at 1 hour and IL-6 max. at 4 hours after reperfusion). Serum procalcitonin is induced as part of the specific SIRS after ILP with rhTNF alpha and melphalan. It may be induced directly by rhTNF alpha or by different cytokines, as serum peaks of IL-6 and IL-8 are reached well before the peak of PCT. Determination of PCT prior to and after ILP with TNF might be useful to assess patients at risk of developing hyperdynamic shock.
 ...
PMID:[Procalcitonin as marker of systemic inflammatory reaction after isolated extremity perfusion]. 1451 84

The aim of this study was to evaluate the systemic and haemodynamic postoperative effects of ILP with medium-low dose of TNF alpha in patients diagnosed with primary or recurrent limb melanoma or sarcoma, and to compare the resulting toxicity with Systemic Inflammatory Response Syndrome (SIRS). A prospective study on 17 consecutive patients with primary or recurrent limb tumor (melanoma or sarcoma) subjected to ILP with escalating doses of TNF alpha (0.5-2.0mg) was carried out. Seventeen patients with primary or recurrent limb melanoma or sarcoma were subjected to ILP with escalating doses of TNF alpha. ILP was carried out with the standard techniques, blood being warmed at 42 degrees C for an hour. Serial serum TNF alpha determinations were performed before, during and after limb perfusion in nine patients. Systemic and pulmonary haemodynamics, by a radial and pulmonary artery catheter inserted before the induction of anesthesia, were monitored at 5 different times: before the induction of anesthesia (T0), and 6, 12, 24 and 48 hours after treatment (T1-4). Complete isolation of the limb was not always achieved, therefore leakage of TNF alpha occurred frequently during the perfusion in all patients with maximum systemic TNF alpha concentrations ranging from 431 to 111000 pg/ml. After perfusion only two patients showed detectable TNF alpha levels in peripheral blood which returned to baseline values within nine hours. These two patients had serious systemic toxicity: shock and respiratory failure secondary to pulmonary edema. Acute pulmonary edema was also observed in another patient. All three cases required supportive therapy provided by means of mechanical ventilation. In the remaining 14 patients a sepsis-like syndrome was observed. The most significant haemodynamic changes were due to the CO, which rose by 35%, and the SVR, which remained consistently low throughout. A reduction in Hb was observed in all patients (with an average decrease of 4 g/dl), while DO2 and VO2 levels rose, though not to statistically significant levels. Hypoxia occurred in all 14 patients. In three of the remaining 14 cases bilateral pulmonary leaks were noted, however the use of mechanical ventilation was not required. No perioperative death occurred and the aforementioned side effects were all reversible resulting in a patient's mean postoperative ICU permanence of 4 days (range 3 to 7 days). In conclusion, ILP with TNF alpha induces cardiovascular, respiratory and hematological toxicity with haemodynamic parameters being similar to those noted in SIRS probably due to leakage of TNF alpha in the systemic circulation during the perfusion. Nevertheless, this systemic toxicity was short-lived resulting in an acute reaction following a single application.
 ...
PMID:Systemic and haemodynamic toxicity after isolated limb perfusion (ILP) with TNF-alpha. 1535 6

A young female with Fisher-Evans' syndrome and a previous melanoma developed acute renal failure with generalized lymphoadenopathy and fever. The appearance of renal lesions is common in the course of several hematological disorders, but is unusual in Fisher-Evans' syndrome. Fisher-Evans' syndrome, defined as Coombs' positive hemolytic anemia and immune thrombocytopenia, is more frequently associated with the other autoimmune diseases, but not with renal involvement. In our case report, having excluded amyloidosis, myeloma, interstitial nephritis and sepsis, the rapid involvement of renal function with enlarged renal size seemed to suggest renal lymphoma. However, the lack of a monoclonal T-lymphocyte population in the renal tissue and peripheral blood, along with a clinical course characterized by a rapid reversibility of acute renal failure made this diagnosis rather an unlikely one. Polyclonal lymphocyte infiltration in a patient with a persistent autoimmune disease made us suspect a hyperimmune reaction. This syndrome is a non-neoplastic proliferation of B-cells involving an exaggeration of lymphocyte transformation. However, the clinical course is progressive and fatal, and can trigger a lymphoproliferative systemic disease. In our patient, two elements led us to suspect it was not a typical hyperimmune syndrome: first, polyclonal lymphocytes had massively infiltrated the kidney and, secondly, the clinical outcome was extremely favorable. Therefore, we were faced with an "atypical" and "singular" hyperimmune reaction with renal involvement, polyclonal proliferation of T-lymphocytes that had exhausted itself over time. Infective or toxic agents or drugs such as cyprofloxacin could have triggered the phenomenon, in the presence of a favorable condition such as Fisher-Evans' syndrome.
 ...
PMID:Acute renal failure in a young woman with Fisher-Evans' syndrome. 1559 44

Medical thoracoscopy is not widely available in Australia. A medical thoracoscopy service has been set up in a regional hospital using no specialized equipment and at minimal cost. Of the first 100 procedures carried out, 89 were for investigation of pleural effusion, 6 for pneumothorax and 6 for empyema. Of the 89 pleural effusions, 73 were diagnosed as malignant (43 carcinoma, 24 mesothelioma, 3 lymphoma, 2 melanoma and 1 sarcoma). The sensitivity for a malignant diagnosis was 94.5%, with 100% specificity. Four patients had unsuspected tuberculous effusions. Pleurodesis was carried out with instillation of dry sterile talc in 67 cases. In 92.5% of these, no further drainage procedure was needed. There was one fatality caused by pre-existing sepsis in a debilitated patient with disseminated carcinoma. Medical thoracoscopy is a simple, safe and cost-effective technique for diagnosing and treating pleural effusions and provides a useful service in the setting of a regional hospital.
 ...
PMID:Medical thoracoscopy in an Australian regional hospital. 1738 68

Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
 ...
PMID:Masquerader: high mobility group box-1 and cancer. 1750 81

Vitiligo-like depigmentation in patients with malignant melanoma is a poorly understood phenomenon. We report a patient who presented with a 4-month history of vitiligo-like depigmentation of the face, trunk and limbs. Physical examination revealed an enlarged left inguinal lymph node. A needle biopsy taken from the lymph nodes revealed metastatic malignant melanoma. One small nodule on the left sole was found subsequently. Despite the absence of junctional activity, it was considered to be a primary tumour with regression of the epidermal lesion. The patient died from sepsis, the main complication of immunosuppressive therapy, without evidence of distant metastasis. We report this case to highlight the importance of careful physical examination of patients with skin hypomelanoses. We also propose that, due to the favourable prognosis in patients with malignant melanomas and vitiligo-like depigmentation, the treatment plan may be more conservative to minimize the adverse effects of chemotherapy.
 ...
PMID:Metastatic malignant melanoma associated with vitiligo-like depigmentation. 2543 33

The use of cultured epithelial autografts (CEA) for the treatment of large burn wounds has gained popularity in recent years. This technique may circumvent the restrictions of limited donor site availability and hasten permanent wound coverage for large TBSA burns. The availability of a large amount of skin from a small donor site with the promise of permanent wound coverage suggests its use in other conditions such as giant congenital nevi (GCN) as well. The risk of malignant transformation of GCN to melanoma although somewhat controversial is significant enough to warrant early excision in childhood. Cultured keratinocytes may provide one-stage coverage of these large wounds, lessening the number of surgeries and the inherent staging problems of tissue expansion or autografting. A retrospective single institution review of was done for 29 children (20 burns and 9 patients with GCN) who underwent coverage of their large surface area wounds with CEA over an 18-year period. Excellent take rates were noted; 76.4% for burn patients and 66% for patients with GCN. Several strategies in preoperative, perioperative, and postoperative care have been standardized and have helped improve outcome. The keys to success with the CEA technique have been aggressive control of wound sepsis, surgical technique, specific use of topical antimicrobials, dressings, and the standardization of nursing and physiotherapy care. Although the cost of CEA is high, the benefits to patient care make this technique an appealing choice for large wound coverage in the pediatric population.
 ...
PMID:Coverage of large pediatric wounds with cultured epithelial autografts in congenital nevi and burns: results and technique. 1950 17

The primary goal of this study was to evaluate the efficacy of immunotherapy for patients with metastatic melanoma with autologous melanoma apoptotic bodies (MAB)-pulsed dendritic cells (DCs). Accessible tumors from eligible patients with refractory metastatic melanoma were surgically removed and processed for primary culture. The autologous tumor cells were treated with dactinomycin to obtain MAB. To generate DCs, adherent peripheral blood mononuclear cells were cultured in complete medium containing granulocyte macrophage-colony stimulating factor and interleukin-4. MAB-pulsed DCs were given either intradermally (i.d.) or intravenously. Patients were immunized at monthly intervals and boosted with keyhole limpet hemocyanin (KLH) and MAB 2 weeks post-vaccination, with a maximum of four cycles. Of the 10 patients enrolled in this trial, nine were treated with MAB-pulsed DCs; two were given intravenous vaccinations and the other seven were i.d. injected. Mild tenderness in the draining lymph nodes lasting for less than 48 h and enlargement of the draining lymph nodes were noted in all seven i.d. cases. Treatment-related grade 3-4 toxicity, neutropenia, skin ulceration, tumor growth at the injection site, and sepsis were not observed in any of the patients. Delayed-type hypersensitivity to KLH was observed in all patients, whereas no delayed-type hypersensitivity to autologous tumor antigens was observed. One patient achieved partial response with reduction in lung metastatic tumor mass, and a presence of vesicles in the post-vaccination KLH response. Two patients had stable disease for more than 24 months; one was still alive at the time of submission of this report, the other eventually developed multiple metastases. MAB-pulsed DC immunotherapy is well tolerated in patients with malignant melanoma; however, its efficacy is only modest. Combination with other modalities is required to enhance DC-based immunotherapy.
Melanoma Res 2009 Oct
PMID:Immunotherapy with dendritic cells pulsed by autologous dactinomycin-induced melanoma apoptotic bodies for patients with malignant melanoma. 1975 May 89

Endothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis, tumor growth, and sepsis. Endothelial cell activation, in turn, is mediated primarily at the level of gene transcription. Here, we show that in response to several activation agonists, including vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha, and thrombin, endothelial cells demonstrate rapid and profound induction of the early growth response (Egr) genes egr-1 and egr-3. In VEGF-treated endothelial cells, induction of Egr-3 was far greater and more prolonged compared with Egr-1. VEGF-mediated stimulation of Egr-3 involved the inducible binding of NFATc, serum response factor, and CREB to their respective consensus motifs in the upstream promoter region of Egr-3. Knockdown of Egr-3 markedly impaired VEGF-mediated proliferation, migration, and tube formation of endothelial cells and blocked VEGF-induced monocyte adhesion. Egr-3 knockdown abrogated VEGF-mediated vascular outgrowth from ex vivo aortic rings and attenuated Matrigel plug vascularization and melanoma tumor growth in vivo. Together, these findings suggest that Egr-3 is a critical determinant of VEGF signaling in activated endothelial cells. Thus, Egr-3 represents a potential therapeutic target in VEGF-mediated vasculopathic diseases.
 ...
PMID:Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3. 2033 6


<< Previous 1 2 3 4 5 6 7 Next >>